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Mutual effects of ablation and ice temperature in a firn-free glacier: Observations from Aug 1st glacier on northeast Tibetan plateau. 青藏高原东北部8月1日冰川消融与冰温的相互影响。
IF 4.1 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-16 eCollection Date: 2026-01-16 DOI: 10.1016/j.isci.2025.114456
Guohua Liu, Rensheng Chen, Chuntan Han, Junfeng Liu, Zhangwen Liu, Yong Yang, Shuihai Guo, Xiqiang Wang, Yiwen Liu, Chanchan Gao

Glacier stability depends on the interaction between ice temperature and ablation, processes mediated by firn cover. Although firn-covered glaciers have been extensively investigated, firn-free glacier dynamics remain less clear. This study analyzes the coupled response of ice temperature and ablation to air temperature on the firn-free Aug 1st glacier in the northeastern Tibetan plateau. Results indicate that surface ice temperature is positively correlated with air temperature; however, without firn to store meltwater, latent heat uptake and runoff-related heat loss reduce the rate of surface warming. Increased ablation also limits heat penetration, encouraging active-layer thinning under stable internal ice temperatures. By contrast, ice temperature has little effect on ablation, which is governed mainly by air temperature. These results advance knowledge of glacier thermal behavior and underscore the importance of glacier type in modeling ice temperature evolution.

冰川的稳定性取决于冰温和消融之间的相互作用,消融过程由雪覆盖介导。尽管积雪覆盖的冰川已被广泛研究,但无积雪冰川的动力学仍然不太清楚。研究了青藏高原东北部8月1日冰川冰温和消融对气温的耦合响应。结果表明:地表冰温与气温呈正相关;然而,如果没有公司储存融水,潜热吸收和径流相关的热损失会降低地表变暖的速度。增加的消融也限制了热穿透,在稳定的内部冰温度下促进活动层变薄。而冰温对烧蚀的影响较小,主要受气温的影响。这些结果促进了对冰川热行为的认识,并强调了冰川类型在模拟冰温度演化中的重要性。
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引用次数: 0
Dinutuximab beta effectively treats Ewing sarcoma when combined with chemotherapy. 迪努妥昔单抗联合化疗可有效治疗尤文氏肉瘤。
IF 4.1 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-16 eCollection Date: 2026-01-16 DOI: 10.1016/j.isci.2025.114449
Roberta Frapolli, Marina Meroni, Ezia Bello, Lorenza Pirona, Elisa Callegari, Valentina Kebede, Isabella Pellerani, Simone Canesi, Eugenio Scanziani, Uta Dirksen, Patrizia Angelico, Stefano Biondi, Matteo Malinverno

Ewing sarcoma is a rare and aggressive cancer of the bone and soft tissues primarily affecting children and young adults. Prognosis for patients with metastatic or recurrent disease remains poor despite intensive multimodal therapy, highlighting the need of novel therapeutic approaches. The disialoganglioside GD2 is highly expressed on Ewing sarcoma cells, making this tumor eligible for anti-GD2 immunotherapy with dinutuximab beta. Through in vitro and in vivo approaches, this study demonstrated that dinutuximab beta effectively suppressed tumor growth by 60% (p = 0.0135) and improved survival rate by 68% (p = 0.0006) in a mouse model xenograft. The combination therapy with doxorubicin demonstrated superior efficacy compared to monotherapy, with enhanced tumor suppression (86%; p = 0.0009) and an extension of survival rate (146%; p = 0.000025). This study showed that dinutuximab beta, particularly in combination with standard chemotherapy, offers a promising approach to improve outcomes for high-risk Ewing sarcoma patients, providing a more effective alternative to current treatments.

尤文氏肉瘤是一种罕见的侵袭性骨和软组织癌症,主要影响儿童和年轻人。尽管进行了强化的多模式治疗,但转移性或复发性疾病患者的预后仍然很差,因此需要新的治疗方法。二联神经节苷脂GD2在尤文氏肉瘤细胞上高表达,使得这种肿瘤适合用迪努妥昔单抗β进行抗GD2免疫治疗。本研究通过体外和体内两种方法证明,在小鼠模型异种移植物中,迪乌妥昔单抗β有效抑制肿瘤生长60% (p = 0.0135),提高生存率68% (p = 0.0006)。与单药治疗相比,阿霉素联合治疗的疗效更好,肿瘤抑制增强(86%,p = 0.0009),生存率延长(146%,p = 0.000025)。本研究表明,迪努妥昔单抗,特别是与标准化疗联合使用,为改善高危尤文氏肉瘤患者的预后提供了一种有希望的方法,为目前的治疗提供了更有效的替代方案。
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引用次数: 0
The myokine musclin in metabolic syndrome: Pathological links and exercise interventions 代谢综合征中的肌素:病理联系和运动干预
IF 4.1 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-16 DOI: 10.1016/j.isci.2025.114367
Ruiming Wen , Yuan Yang , Haixia Wang , Yikun Teng , Bing Zhao , Hanxiao Zhu , Songtao Wang
Since its identification in 2004, the myokine Musclin, a skeletal muscle-specific secretory factor, has garnered increasing attention in the fields of metabolism and exercise medicine due to its pleiotropic regulatory functions. This review proposes and substantiates the central thesis that Musclin acts as a “bidirectional hub” connecting exercise and metabolic homeostasis. Under physiological conditions, the pulsatile secretion of Musclin promotes mitochondrial biogenesis and enhances exercise endurance. In contrast, during pathological states, its overexpression exacerbates metabolic disorders by interfering with insulin signaling, inducing endoplasmic reticulum stress (ERS), and suppressing adipose thermogenesis. A body of evidence indicates that the expression and function of Musclin are precisely regulated by genetic, nutritional, and exercise-related factors, underscoring its pivotal role in the systemic metabolic network. Although its elevated levels may be perceived as a compensatory response in certain contexts, gain-of-function experiments and other evidence posit that Musclin primarily acts as a “pathological driver,” demonstrating context-dependent effects in obesity, type 2 diabetes mellitus (T2DM), hypertension, and other components of metabolic syndrome (MetS). Current research in the field faces challenges, including sample heterogeneity, lack of standardized detection methods, and a translational gap between animal models and human diseases. Therefore, this review systematically integrates the molecular characteristics, pathophysiological effects, and exercise adaptation mechanism of Musclin, and reveals its “bidirectional hub” role in metabolic homeostasis.
肌因子Musclin是一种骨骼肌特异性分泌因子,自2004年被发现以来,由于其多效调节功能,在代谢和运动医学领域受到越来越多的关注。这篇综述提出并证实了Musclin作为连接运动和代谢稳态的“双向枢纽”的中心论点。在生理条件下,搏动性分泌Musclin促进线粒体生物发生,提高运动耐力。相反,在病理状态下,它的过表达通过干扰胰岛素信号、诱导内质网应激(ERS)和抑制脂肪产热而加剧代谢紊乱。大量证据表明,Musclin的表达和功能受到遗传、营养和运动相关因素的精确调节,强调了其在全身代谢网络中的关键作用。虽然在某些情况下,其水平升高可能被认为是一种代偿反应,但功能获得实验和其他证据表明,Musclin主要作为一种“病理驱动因素”,在肥胖、2型糖尿病(T2DM)、高血压和代谢综合征(MetS)的其他组成部分中显示出环境依赖性作用。目前该领域的研究面临挑战,包括样本异质性,缺乏标准化的检测方法,以及动物模型与人类疾病之间的翻译差距。因此,本文系统整合了Musclin的分子特征、病理生理作用和运动适应机制,揭示了其在代谢稳态中的“双向枢纽”作用。
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引用次数: 0
A method for cryo-EM analysis of eukaryotic nucleosomes reconstituted in bacterial cells. 细菌细胞中重组真核小体的低温电镜分析方法。
IF 4.1 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-16 eCollection Date: 2026-01-16 DOI: 10.1016/j.isci.2025.114453
Cheng-Han Ho, Yuki Kobayashi, Mitsuo Ogasawara, Yoshimasa Takizawa, Hitoshi Kurumizaka

Conventional methods for preparing nucleosomes are time-consuming and technically demanding. In the present study, we extended the approach of generating nucleosomes in Escherichia coli by the co-expression of all four histones, allowing nucleosomes to be assembled in cells. The bacterially reconstituted nucleosomes can be readily prepared from the E. coli cells and directly subjected to cryo-EM single particle analysis. Using this method, we obtained a 2.56 Å nucleosome structure that is highly similar to a previously reported nucleosome crystal structure, validating the use of nucleosomes formed in E. coli for cryo-EM analysis. Unexpectedly, we also discovered a non-canonical nucleosome structure, in which two hexasomes are closely packed. This system provides a robust and efficient platform for structural studies of nucleosomes and nucleosome variants, and may facilitate the discovery of chromatin architectures.

制备核小体的传统方法耗时且技术要求高。在本研究中,我们扩展了在大肠杆菌中通过共表达所有四种组蛋白来产生核小体的方法,使核小体能够在细胞中组装。细菌重组的核小体可以很容易地从大肠杆菌细胞中制备,并直接进行低温电镜单颗粒分析。使用这种方法,我们获得了2.56 Å核小体结构,与先前报道的核小体晶体结构高度相似,验证了在大肠杆菌中形成的核小体用于冷冻电镜分析的可行性。出乎意料的是,我们还发现了一个非典型核小体结构,其中两个六体紧密排列。该系统为核小体和核小体变异的结构研究提供了一个强大而有效的平台,并可能促进染色质结构的发现。
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引用次数: 0
Spectrin condensates provide a nidus for assembling the axonal membrane-associated periodic skeleton. 谱质凝聚体为轴突膜相关周期骨架的组装提供了一个中心。
IF 4.1 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-16 eCollection Date: 2026-01-16 DOI: 10.1016/j.isci.2025.114454
Nicholas P Boyer, Rohan Sharma, Theresa Wiesner, Christopher Parperis, Antoine Delamare, Florence Pelletier, Nicolas Jullien, Anshul M Bhatt, Leonardo A Parra-Rivas, Patrick J Kearney, Farbod Shavarebi, Christophe Leterrier, Subhojit Roy

In axons, α/β-spectrins, adducin, and actin filaments assemble into a lattice underneath the plasma membrane, but the mechanistic events leading to this membrane-associated periodic skeleton (MPS) are unclear. Visualizing MPS-components in developing axons, we found distal focal patches containing spectrins and adducin (but sparse actin filaments) with biophysical properties reminiscent of biomolecular condensation. Overexpressing spectrin repeats - constituents of α/β-spectrins - in heterologous cells triggered condensate formation, and preventing the association of βII-spectrin with actin filaments or membranes also facilitated condensation. Introducing a stretch of spectrin-repeats in neurons before MPS establishment triggered ectopic condensate-like structures in the soma and disrupted the axonal lattice, advocating a functional role for biomolecular condensation. We propose a condensation-assembly model where spectrin-repeats trigger focal phase separated condensates, providing a nidus for MPS assembly that recruits actin filaments to ultimately generate the stable lattice. Our overall model is supported by recent studies showing phase-separation via coiled-coil domains and recruitment/polymerization of actin by other condensate-forming proteins.

在轴突中,α/β-谱蛋白、内收蛋白和肌动蛋白丝在质膜下组装成晶格,但导致这种膜相关周期性骨架(MPS)的机制尚不清楚。通过观察发育中的轴突中的mps组分,我们发现远端焦斑含有谱蛋白和内收蛋白(但稀疏的肌动蛋白丝),其生物物理特性让人想起生物分子凝聚。在异源细胞中过度表达α/β-spectrin重复序列会引发凝析物的形成,而阻止βII-spectrin与肌动蛋白丝或膜的结合也会促进凝析物的形成。在MPS建立之前,在神经元中引入一段谱重复序列,触发了体细胞中的异位凝聚样结构,破坏了轴突晶格,倡导生物分子凝聚的功能作用。我们提出了一个凝聚-组装模型,其中光谱重复触发焦点相分离凝聚,为MPS组装提供了一个中心,招募肌动蛋白丝最终产生稳定的晶格。我们的整体模型得到了最近研究的支持,这些研究表明,通过线圈结构域进行相分离,以及其他凝聚形成蛋白对肌动蛋白的招募/聚合。
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引用次数: 0
Selective deletion of Slc2a1 from the RPE reveals that rods but not cones depend on glucose transport across the outer blood-retinal barrier. RPE中Slc2a1的选择性缺失表明,视杆细胞而非视锥细胞依赖于通过血液-视网膜外屏障的葡萄糖运输。
IF 4.1 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-16 eCollection Date: 2026-01-16 DOI: 10.1016/j.isci.2025.114450
Lauren L Daniele, John Y S Han, Minzhong Yu, Ravi A Sangani, Craig D Beight, Cyrus Rostami, Philip D Kiser, Neal S Peachey, Nancy J Philp

GLUT1 facilitates a continuous flow of glucose across the inner and outer blood-retinal barriers (BRBs) to support vision. To understand the extent to which photoreceptors rely on glucose transport across the outer BRB, we generated a tamoxifen-inducible conditional knockout of Slc2a1 in the retinal pigment epithelium (RPE) (RPE-iΔGlut1). In the RPE-iΔGlut1 mice, rod photoreceptors exhibited impaired outer segment renewal and decreased the expression of proteins involved in phototransduction and ciliary transport. Proteins regulating the retinal stress response increased. Cone photoreceptors were functional and viable 15 months post-tamoxifen treatment in the RPE-iΔGlut1 mice, while 70% of the rods died. When Slc2a1 was genetically deleted from rods (Rod-iΔGlut1 mice), rod degeneration was faster than in the RPE-iΔGlut1 mice. These findings suggest that rods are more dependent on glucose than cones, and that glucose from the deep vascular plexus may support cone function and viability and slow the rate of rod death.

GLUT1促进葡萄糖通过血液和视网膜屏障(brb)的连续流动,以支持视力。为了了解光感受器在多大程度上依赖于葡萄糖通过外部BRB的运输,我们在视网膜色素上皮(RPE)中产生了他莫昔芬诱导的条件敲除Slc2a1 (RPE-iΔGlut1)。在RPE-iΔGlut1小鼠中,杆状光感受器表现出外节更新受损,参与光传导和纤毛运输的蛋白质表达减少。调节视网膜应激反应的蛋白质增加。他莫昔芬治疗RPE-iΔGlut1小鼠15个月后,视锥细胞的光感受器功能正常,存活,而70%的视杆细胞死亡。当从杆状体(Rod-iΔGlut1小鼠)中基因删除Slc2a1时,杆状体的退化速度比RPE-iΔGlut1小鼠快。这些发现表明,视杆细胞比视锥细胞更依赖葡萄糖,来自深血管丛的葡萄糖可能支持视锥细胞的功能和活力,并减缓视杆细胞的死亡速度。
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引用次数: 0
Size-dependent pyroptosis induction by calcium oxalate monohydrate crystals in HK-2 cells. 草酸钙一水晶体诱导HK-2细胞大小依赖性焦亡。
IF 4.1 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-16 eCollection Date: 2026-01-16 DOI: 10.1016/j.isci.2025.114459
Xue-Wu Chen, Xin-Yi Tong, Run-Min Tan, Jian-Ming Ouyang

This article explored the differences in pyroptosis mediated by calcium oxalate monohydrate (COM) crystals with sizes of 100 nm, 1 μm, 3 μm, 5 μm, and 10 μm and were used to induce pyroptosis of HK-2 cells. The proportion of pyroptosis cells was detected by caspase-1/PI double staining. Three small-sized COM crystals (0.1-3 μm) could be endocytosis by HK-2 cells and increased intracellular oxidative stress, which further promoted the activation of NLRP3 inflammasome and pyroptosis. The two COM crystals with large sizes (3-10 μm) were difficult to endocytose, and the main mechanism was the crystal adhesion, leading to pyroptosis. Crystal endocytosis leads to higher pyroptosis. The pyroptosis rates mediated by COM with different sizes were as follows: COM-100nm (17.81%) > COM-1μm (17.28%) > COM-3μm (17.25%) > COM-5μm (12.44%) > COM-10μm (9.05%). The smaller the COM crystal size, the higher the pyroptosis rate, which is related to the stronger oxidative stress.

研究了100 nm、1 μm、3 μm、5 μm、10 μm大小的草酸钙晶体诱导HK-2细胞焦亡的差异。采用caspase-1/PI双染色法检测焦亡细胞比例。3个小尺寸COM晶体(0.1 ~ 3 μm)可被HK-2细胞内吞,增加细胞内氧化应激,进一步促进NLRP3炎性体的活化和焦亡。两种尺寸较大(3 ~ 10 μm)的COM晶体难以内吞,其主要机制是晶体黏附导致焦亡。晶体内吞作用导致较高的焦亡。COM-100nm(17.81%)、> COM-1μm(17.28%)、> COM-3μm(17.25%)、> COM-5μm(12.44%)、> COM-10μm(9.05%)介导的焦亡率分别为:COM-100nm(17.81%)、> COM-1μm(17.28%)。COM晶体尺寸越小,焦亡率越高,这与氧化应激越强有关。
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引用次数: 0
Interpretable machine learning for accessible dysphagia screening and staging in older adults. 可解释的机器学习在老年人吞咽困难筛查和分期中的应用。
IF 4.1 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-16 eCollection Date: 2026-01-16 DOI: 10.1016/j.isci.2025.114451
Yinuo Dai, Jianzheng Cai, Zhina Gong, Chunyan Niu, Weixia Yu, Haifang Wang, Yingying Zhang

Dysphagia in older adults causes serious complications, and efficient and scalable screenings are needed. This prospective multicenter study developed interpretable machine learning (ML) models for the early identification and staging of dysphagia. Nine ML models were built using the clinical data from 1,235 patients and externally validated on 720 patients. All patients were older adults from seven Suzhou hospitals whose dysphagia was confirmed via videofluoroscopic swallowing studies. Features were selected via random forest, and model interpretability was analyzed with SHapley Additive exPlanations (SHAP). The CatBoost model achieved an area under the receiver operating characteristic curve (AUC) of 0.914 for binary classification, while neural network gave AUC 0.884 for multiclass classification. External validation confirmed robustness (binary AUC, 0.909 and multiclass macro-AUC, 0.860). SHAP identified ten core features-oral/pharyngeal function influenced all stages, and masticatory/phonatory features acted selectively. A web application was created accordingly to facilitate real-time screening and stratify dysphagia patients.

老年人吞咽困难会导致严重的并发症,需要有效和可扩展的筛查。这项前瞻性多中心研究开发了可解释的机器学习(ML)模型,用于吞咽困难的早期识别和分期。利用1235例患者的临床数据建立了9个ML模型,并对720例患者进行了外部验证。所有患者均为来自苏州七家医院的老年人,通过视频透视吞咽检查确认吞咽困难。通过随机森林选择特征,并使用SHapley加性解释(SHAP)分析模型的可解释性。CatBoost模型对二类分类的接收者工作特征曲线下面积(AUC)为0.914,神经网络对多类分类的AUC为0.884。外部验证证实了稳健性(二元AUC为0.909,多类宏观AUC为0.860)。SHAP确定了十个核心特征-口腔/咽功能影响所有阶段,咀嚼/发音特征选择性地起作用。因此,创建了一个web应用程序,以方便实时筛查和分层吞咽困难患者。
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引用次数: 0
A potential application of dual-mode metafilm for enhanced second harmonic generation in refractive index and angle measurement. 双模元膜在折射率和角度测量中增强二次谐波产生的潜在应用。
IF 4.1 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-15 eCollection Date: 2026-01-16 DOI: 10.1016/j.isci.2025.114448
Xiang Li, Jun-Yang Sui, Hai-Feng Zhang

Second harmonic generation (SHG) is a nonlinear phenomenon in which incident electromagnetic wave signals are converted into harmonic signals with doubled frequency. In this paper, a method has been proposed to enhance the SHG using metafilm, enabling the measurement of refractive index and incident angle. Metafilm refers to artificially constructed layered structures. Nonlinear frequency conversion within metafilms yields dual-mode harmonics, which can effectively distinguish the refractive index of sample layers. When the sample layer is composed of biomedical materials, the fundamental mode can distinguish enamel from dentin, while the second harmonic mode can effectively distinguish normal cells from cancerous cells. Finally, we consider the influences of thickness errors and material losses on detection performance and find that the system has good stability. This non-contact measurement method with extended range shows broad application prospects in the fields of biological tissue composition analysis and medical diagnosis.

二次谐波产生是入射电磁波信号转换成倍频谐波信号的一种非线性现象。本文提出了一种利用元膜增强SHG的方法,实现了折射率和入射角的测量。元膜是指人工构建的层状结构。元膜内部的非线性频率转换产生双模谐波,可以有效地区分样品层的折射率。当样品层由生物医学材料组成时,基频模式可以区分牙本质和牙釉质,次谐波模式可以有效区分正常细胞和癌细胞。最后,考虑了厚度误差和材料损耗对检测性能的影响,系统具有良好的稳定性。这种非接触式测量方法具有较大的测量范围,在生物组织成分分析和医学诊断等领域具有广阔的应用前景。
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引用次数: 0
Transcranial microtesla magnetic fields suppress neuroinflammation and neuronal oxidative stress burden. 经颅微特斯拉磁场抑制神经炎症和神经元氧化应激负担。
IF 4.1 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-15 eCollection Date: 2026-01-16 DOI: 10.1016/j.isci.2025.114425
Nhu Nguyen, Nathan R Brady, Greg A Timblin, Kevin M Tharp, Blake T Gurfein

Neuroinflammation is a major driver of neurodegenerative and psychiatric disease, yet current therapies have limited brain penetration and efficacy. We investigated microtesla magnetic therapy (MMT), a brief transcranial exposure to time-varied electromagnetic fields (TV-EMFs), as a noninvasive approach to modulate neuroimmune inflammation. In human peripheral blood mononuclear cells, MMT suppressed lipopolysaccharide (LPS)-induced TNFα and IL-1β release and reduced NF-κB activation in monocyte and macrophage lines. In rats with intracerebral LPS injection, a model of progressive neuroinflammation, repeated head-localized MMT markedly decreased microgliosis, astrogliosis, and lesion size. In a neuron-immune cell model, MMT reduced cytokine-driven and paraquat-induced oxidative stress, producing both indirect and direct neuroprotection lasting up to 48 h. Collectively, these findings validate transcranial MMT as a promising, noninvasive biophysical therapy for neuroinflammatory conditions. Both acute and repetitive TV-EMF protocols delivered robust anti-inflammatory, antioxidant, and neuroprotective effects, demonstrating the therapeutic potential of precisely modulated EMFs to safely manage neuroinflammation.

神经炎症是神经退行性疾病和精神疾病的主要驱动因素,但目前的治疗方法对大脑的渗透和疗效有限。我们研究了微特斯拉磁疗(MMT),一种短暂的经颅时变电磁场(电视- emf)暴露,作为调节神经免疫炎症的非侵入性方法。在人外周血单核细胞中,MMT抑制脂多糖(LPS)诱导的TNFα和IL-1β的释放,降低单核细胞和巨噬细胞中NF-κB的活化。在脑内注射LPS的大鼠中,进行性神经炎症模型,反复头部定位MMT显着减少小胶质细胞增生,星形胶质细胞增生和病变大小。在神经元免疫细胞模型中,MMT降低了细胞因子驱动和百草枯诱导的氧化应激,产生了持续48小时的间接和直接神经保护。总的来说,这些发现证实了经颅MMT是一种有前途的、无创的神经炎症生物物理治疗方法。急性和重复电视电磁场方案都具有强大的抗炎、抗氧化和神经保护作用,证明了精确调节电磁场在安全管理神经炎症方面的治疗潜力。
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引用次数: 0
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